1. Field of the Invention
The present invention relates to transcellular transport or cellular uptake of vitamin C (L-ascorbate), and in particular to compositions encoding transport proteins for vitamin C and methods for its preparation and use.
2. Background Information
Vitamin C is an essential multi-functional micronutrient required in its reduced form (L-ascorbic acid) for many enzymatic reactions and as a scavenger of free radicals generated from numerous physiological and pathological processes. It has been known for more than 70 years that vitamin C is essential to the human body, and the disease scurvy, caused by an extreme deficiency of vitamin C, has been known for hundreds of years. But surprisingly, little has heretofore been discovered about how the body actually absorbs vitamin C, and how the vitamin is distributed to the many organs at appropriate concentrations to ensure crucial enzymatic reactions (e.g., collagen synthesis) and to protect tissues and organs from oxidative damage.
Several facilitative hexose transporters (of the GLUT family) are known to transport dehydroascorbic acid (but not L-ascorbic acid) in vitro. Although the oxidized form of the vitamin has the same oral bioactivity as L-ascorbic acid, the GLUT-type transporters are unlikely to account for significant absorption of the vitamin as long as glucose is present in the lumen. Whereas several human cell types have been shown to possess high capacity dehydroascorbic acid transport activity in vitro, these systems may have only limited physiological significance because vitamin C is present in human plasma essentially only in its reduced form, so the GLUT systems would not be expected to participate in the cellular uptake of the vitamin. The exception is in the “recycling” of the oxidized vitamin, e.g., in activated neutrophils or erythrocytes, under conditions in which the extracellular dehydroascorbic acid concentration may be locally high.
There are numerous suggestions in the literature regarding the involvement of vitamin C in a variety of human diseases. Studies indicate that vitamin C levels are reduced in the elderly, smokers, and cancer patients, and that defective serum antioxidant status contributes to the increased oxidative stress associated with many diseases. For example, oxidative stress in the central nervous system (CNS) may cause oxidation of lipoprotein, which can itself initiate the neuronal cell death leading to the manifestation of neurodegenerative diseases. Epidemiological research suggests that dietary vitamin C supplementation is effective in the prevention of various types of cancer, including bladder, breast, cervical, colorectal, esophageal, lung, pancreatic, prostate, salivary gland, stomach, leukemia, and non-Hodgkin's lymphoma. Vitamin C may also play a protective role in atherogenesis, since epidemiological studies indicate that plasma ascorbic acid levels are inversely related to mortality due to coronary heart disease.